INTRODUCTION: The phase 3 CLEAR study demonstrated that lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma (RCC). Prognostic features including presence and/or site of baseline metastases, prior nephrectomy, and sarcomatoid features have been associated with disease and treatment success. This subsequent analysis explores outcomes in patients with or without specific prognostic features. METHODS: In CLEAR, patients with clear cell RCC were randomly assigned (1:1:1) to receive either lenvatinib (20 mg/day) plus pembrolizumab (200 mg every 3 weeks), lenvatinib (18 mg/day) plus everolimus (5 mg/day), or sunitinib alone (50 mg/day, 4 weeks on, 2 weeks off). In this report, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were all assessed in the lenvatinib-plus-pembrolizumab and the sunitinib arms, based on baseline features: lung metastases, bone metastases, liver metastases, prior nephrectomy, and sarcomatoid histology. RESULTS: In all the assessed subgroups, median PFS was longer with lenvatinib-plus-pembrolizumab than with sunitinib treatment, notably among patients with baseline bone metastases (HR 0.33, 95% CI 0.21-0.52) and patients with sarcomatoid features (HR 0.39, 95% CI 0.18-0.84). Median OS favored lenvatinib plus pembrolizumab over sunitinib irrespective of metastatic lesions at baseline, prior nephrectomy, and sarcomatoid features. Of interest, among patients with baseline bone metastases the HR for survival was 0.50 (95% CI 0.30-0.83) and among patients with sarcomatoid features the HR for survival was 0.91 (95% CI 0.32-2.58); though for many groups, median OS was not reached. ORR also favored lenvatinib plus pembrolizumab over sunitinib across all subgroups; similarly, complete responses also followed this pattern. CONCLUSION: Efficacy outcomes improved following treatment with lenvatinib-plus-pembrolizumab versus sunitinib in patients with RCC-irrespective of the presence or absence of baseline lung metastases, baseline bone metastases, baseline liver metastases, prior nephrectomy, or sarcomatoid features. These findings corroborate those of the primary CLEAR study analysis in the overall population and support lenvatinib plus pembrolizumab as a standard of care in 1L treatment for patients with advanced RCC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT02811861.

Barts Cancer Institute and the Royal Free Hospital Queen Mary University of London London United Kingdom

Biostatistics Eisai Inc Nutley NJ United States

Clinic for Medical Oncology and Clinic for Urology University Hospital Essen Essen Germany

Clinical Research Eisai Inc Nutley NJ United States

Clinical Research Eisai Ltd Hatfield United Kingdom

Clinical Research Merck and Co Inc Rahway NJ United States

Department of Biomedical Sciences and Human Oncology University of Bari 'A Moro' Bari Italy

Department of Internal Medicine Yonsei Cancer Center Yonsei University Health System Seoul Republic of Korea

Department of Medical Oncology Dana Farber Cancer Institute Boston MA United States

Department of Medical Oncology Hospital de la Santa Creu i Sant Pau Barcelona Spain

Department of Medicine Memorial Sloan Kettering Cancer Center New York NY United States

Department of Oncology Charles University and Thomayer University Hospital Prague Czechia

Department of Oncology Maimonides Institute for Biomedical Research of Córdoba Hospital Universitario Reina Sofía Córdoba Spain

Department of Oncology University of Western Ontario London ON Canada

Department of Urology Kyushu University Fukuoka Japan

Department of Urology Seoul St Mary's Hospital The Catholic University of Korea Seoul Republic of Korea

Department of Urology Tokyo Women's Medical University Tokyo Japan

Global Clinical Development Merck and Co Inc Rahway NJ United States

ICON Research South Brisbane and University of Queensland St Lucia QLD Australia

Medical Oncology Texas Oncology Dallas TX United States

State Institution of Healthcare Regional Clinical Oncology Dispensary Omsk Russia

Front Oncol. 2024 Mar 01;13:1343027. doi: 10.3389/fonc.2023.1343027. PubMed

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ClinicalTrials.gov
NCT02811861